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A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
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ASK1 Regulates Bleomycin-induced Pulmonary Fibrosis.
Samuel S Valenca1, Brittany E Dong1, Elizabeth M Gordon1
1Department of Physiology.
American Journal of Respiratory Cell and Molecular Biology
|February 11, 2022
Summary
Apoptosis signal-regulating kinase-1 (ASK1) inhibition reduces pulmonary fibrosis (PF) in mice. Blocking ASK1 improved survival and lung function, suggesting ASK1 is a key target for treating PF.
Area of Science:
- Cell Biology
- Molecular Biology
- Pathology
Background:
- Pulmonary fibrosis (PF) involves lung tissue remodeling, inflammation, and apoptosis.
- Apoptosis signal-regulating kinase-1 (ASK1) is activated by oxidative stress and promotes inflammation and apoptosis.
Purpose of the Study:
- To investigate the role of ASK1 in bleomycin-induced pulmonary fibrosis.
- To evaluate the therapeutic potential of ASK1 inhibition in PF.
Main Methods:
- Utilized Ask1 knockout (Ask1-/-) mice and wild-type (WT) mice.
- Induced pulmonary fibrosis using bleomycin.
- Administered an ASK1 inhibitor, selonsertib (GS-4997), to WT mice.
Main Results:
- Ask1-/- mice showed reduced PF, improved survival, and restored lung function compared to WT mice.
- Bleomycin induced ASK1, p38, and ERK1/2 activation, altered redox indicators, and increased collagen and EMT markers in WT mice.
- ASK1 inhibition with selonsertib attenuated these changes and improved histological parameters in WT mice.
Conclusions:
- ASK1 plays a critical role in bleomycin-induced pulmonary fibrosis development through p38 and ERK1/2 signaling.
- Targeting the ASK1/p38/ERK1/2 axis represents a potential therapeutic strategy for pulmonary fibrosis.
